Yogurt is generally recognized as a beneficial food for our health, but research into its physiological effects has focused mainly on intestinal dysfunctions such as constipation and diarrhea. We previously found yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 (hereafter OLL1073R-1) could reduce risks of catching the common cold and flu in human trials. It was assumed that immunostimulatory exopolysaccharide (EPS) produced from OLL1073R-1 play an important role in this context. However, few studies have examined the immunostimulatory effects of traditional Bulgarian yogurts fermented with different strains of lactobacilli and their metabolites. Therefore, we screened 139 L. delbrueckii ssp. bulgaricus strains and identified OLL1073R-1 as the most robust producer of EPS. This strain was also the only strain that induced the production of IFN-γ in vitro. Oral administration of the EPS or yogurt fermented with OLL1073R-1 and Streptococcus thermophilus OLS3059 (OLL1073R-1 yogurt) augmented natural killer (NK) cell activity and induced IFN-γ production in spleen cells in mice, whereas 2 other yogurts fermented with other strains had no effect on NK cell activity. Cellular preparations of the OLL1073R-1 strain also slightly augmented NK cell activity, but were less effective than EPS itself. The EPS-dependent stimulation of NK cell activity was abrogated in IFN-γ knockout mice and in myeloid differentiation factor 88 knockout mice. Furthermore, IFN-γ production from spleen cells stimulated with EPS was completely blocked with both anti-IL-12 and anti-IL-18 antibodies in vitro. These findings suggest that NK cell activation by OLL1073R-1 yogurt is EPS-dependent, occurs via IL-12- and IL-18-mediated IFN-γ production, and requires myeloid differentiation factor 88. We showed that traditional Bulgarian yogurt could exert immunostimulatory effects by selecting starter strains and part of the mechanisms depend on IFN-γ inducible EPS produced from L. delbrueckii ssp. bulgaricus. Further investigations on processes of fermentation to increase of the EPS may lead to the development of new functional foods that keep our immune functions stable.

Immunoregulatory probiotics (immunobiotics) have been proposed to improve piglets’ immune system to avoid intestinal infections and reduce unproductive inflammation after weaning. Previously, it was demonstrated that Lactobacillus jensenii TL2937 (LjTL2937) attenuated the inflammatory response triggered by activation of Toll-like receptor 4 (TLR-4) in porcine intestinal epithelial (PIE) cells and antigen presenting cells (APCs) from porcine Peyer’s patches (PP). In view of the critical importance of PIE-APCs interactions in the regulation of intestinal immune responses, we aimed to examine the effect of LjTL2937 on activation patterns of APCs from swine PPs in co-cultures with PIE cells. In addition, we investigated whether LjTL2937 was able to beneficially modulate intestinal immunity of piglets after weaning to improve immune-health status. Stimulation of PIE-APCs co-cultures with LjTL2937 increased the expression of MHC-II, CD80/86, IL-10, and Bcl-3 in CD172a⁺CD11R1^- and CD172a⁺CD11R1^high APCs. In addition, the TL2937 strain caused the upregulation of three negative regulators of TLR4 in PIE cells: MKP-1, Bcl-3 and A20. These changes significantly reduced the inflammatory response triggered by TLR4 activation in PIE-APCs co-cultures. The in vivo experiments using castrated male piglets (crossbreeding (LWD) with Landrace (L), Large Yorkshire (W) and Duroc (D))of 3 weeks of age demonstrated that feeding with LjTL2937 significantly reduced blood complement activity and C reactive protein concentrations while no changes were observed in blood leukocytes, ratio of granulocytes to lymphocyte numbers, macrophages’ activity and antibody levels. In addition, treatment with LjTL2937 significantly improved growth performance and productivity, and increased carcass quality. We demonstrated that the use of immunobiotics strains like LjTL2937, as supplemental additives for piglets feedings, could be used as a strategy to maintain and improve intestinal homeostasis; that is important for the development of the pig and for health and performance throughout the productive life of the animal.

Lactic acid bacteria (LAB) form a major component of gut microbiota and are often used as probiotics for fermented foods, such as yoghurt. In this study, we aimed to evaluate immunomodulatory activity of LAB, especially that of Lactobacillus bulgaricus ME-552 (ME552) and Streptococcus thermophilus ME-553 (ME553). In vivo/in vitro assay was performed in order to investigate their effects on T cell function. After oral administration of ME553 to C57BL/6 mice, the amount of both interferon γ (IFN-γ) and interleukin 17 (IL-17) produced by cluster of differentiation (CD) 4⁺ T cells from Peyer’s patches (PPs) were significantly enhanced. On the other hand, ME552 only up-regulated the production of IL-17 from PP cells. The extent of induction for IFN-γ production differed between ME552 and ME553. These results suggest that LAB modulate T cell effector functions and mucosal immunity.

Fatigue caused by summer heat is a typical indefinite complaint along with anorexia, loss of sleep, stress, lack of motivation and, in some cases, catching a cold. Yogurt fermented with Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1 has been shown to stimulate the immune system and reduce the risk of catching colds. Here, we conducted a randomized, double-blinded, placebo-controlled trial to investigate whether ingesting this yogurt could ameliorate summer heat fatigue in 49 healthy males (median age 40.0 ± 6.0 years; 30–49 years) who felt fatigued every summer. Fatigue was evaluated by visual analogue scales (VAS) and the balance of sympathetic/parasympathetic nervous systems. After 12 weeks of ingestion in early autumn, the VAS fatigue scores in the yogurt group were lower than those of the placebo group. These results indicate that yogurt fermented with L. bulgaricus OLL1073R-1 can ameliorate summer heat fatigue lasting up to early autumn.

Immunobiotic Lactobacillus jensenii TL2937 modulates porcine mononuclear phagocytes from Peyer’s patches (PPMPs) and induces a differential production of pro- and anti-inflammatory cytokines in response to Toll-like receptor (TLR)-4 activation. In view of the important role played by phagocytosis in the activation of antigen presenting cells (APCs), the aim of the present work was to examine the interaction of TL2937 with porcine PPMPs focusing on phagocytosis. In addition, this study aimed to investigate whether the effects of L. jensenii TL2937 in porcine blood monocyte-derived dendritic cells (MoDCs) are similar to those found in PPMPs considering that MoDCs do not recapitulate all functions of mucosal APCs. Studies showed a high ability of porcine CD172a+ PPMPs to phagocytose L. jensenii TL2937. Interestingly, our results also revealed a reduced capacity of the non-immunomodulatory L. plantarum TL2766 to be phagocytosed by those immune cells. Phagocytosis of L. jensenii TL2937 by porcine PPMPs was partially dependent on TLR2. In addition, we demonstrated that TL2937 strain was able to improve the expression of IL-1β, IL-12 and IL-10 in immature MoDCs resembling the effect of this immunobiotic bacterium on PPMPs. Moreover, similarly to PPMPs those immunomodulatory effects were related to the higher capacity of TL2937 to be phagocytosed by immature MoDCs. Microbial recognition in APCs could be effectively mediated through ligand-receptor interactions that then mediate phagocytosis and signaling. For the immunobiotic strain TL2937, TLR2 has a partial role for its interaction with porcine APCs and it is necessary to investigate the role of other receptors. A challenge for future research will be advance in the full understanding of the molecular interactions of immunobiotic L. jensenii TL2937 with porcine APCs that will be crucial for the successful development of functional feeds for the porcine host. This study is a step in that direction.

The significance of less abundant genera within the gut microbiota, such as Parabacteroides, remains largely unexplored. Despite its low levels, Parabacteroides is highly conserved and potentially beneficial across populations. This trial aimed to evaluate whether a four-week intake of glucolacto-oligosaccharides (GLO), previously reported as an enhancer of Parabacteroides, improves defecation frequency as the primary outcome. It also assessed holistic gut health and underlying microbiota-based mechanisms. In this randomized, double-blind, placebo-controlled trial, 50 healthy Japanese participants with a defecation frequency of five or fewer times per week were enrolled. The mean (±SE) weekly defecation frequency in the GLO group was 3.2 ± 0.2 at baseline, increasing to 5.8 ± 0.6 at week 4, whereas that in the placebo group was 3.4 ± 0.3 at baseline, increasing to 4.4 ± 0.3 at week 4. The time-dependent weekly defecation frequency was significantly higher in the GLO group than in the placebo group (p = 0.029). Changes in the relative abundance of the genus Parabacteroides significantly increased in the GLO group compared with in the placebo group. Changes in fecal bile acid composition were also confirmed in the GLO group compared with the placebo group, which was thought to be due to the unique features of Parabacteroides. Furthermore, changes in alpha diversity indices were significantly higher in the GLO group than in the placebo group (Simpson, p = 0.041; Pielou, p = 0.022). Additional analysis demonstrated that the increase in alpha diversity in the GLO group was significantly correlated with the increase in the relative abundance of Parabacteroides (p = 0.006), which tended to be associated with decreases in serum gamma-glutamyltransferase (p = 0.089) and serum triglyceride (p = 0.075) levels. These data suggest that GLO intake improved defecation status, selectively increased Parabacteroides, and harmonized the gut environment.